Once-daily Tiotropium ( Spiriva ) Respimat, a long-acting anticholinergic bronchodilator, has been shown in a phase III program to improve lung function and reduce severe exacerbation risk in severe asthma patients who remain symptomatic despite using ICS+LABA.
Use of pre-trial leukotriene receptor antagonists ( LTRAs ) was not restricted.
Researchers analyzed whether pre-screening LTRA use affected Tiotropium Respimat efficacy.
In two phase III, replicate, randomized, double-blind, placebo-controlled, parallel-group trials, symptomatic patients received high-dose ICS+LABA and once-daily Tiotropium Respimat 5 mcg or placebo.
LTRAs were permitted during run-in and treatment.
Co-primary endpoints were peak and trough FEV1 response ( difference from baseline ) at 24 weeks. Subgroups were defined by pre-screening LTRA use: Yes/No.
Of 912 randomized patients, 205 reported pre-screening LTRA use, 200 reported use during the treatment period, and 187 had efficacy data at week 24.
Baseline characteristics were comparable between groups. Mean BMI in LTRA Yes/No groups: 27.8 kg/m2 and 28.3 kg/m2, respectively.
Mean % predicted FEV1 at baseline: 56% in both groups.
Lung function responses improved independent of LTRA use: peak FEV1 was 99±50 mL ( p=0.049 ) in the LTRA Yes group, and 113±28 mL ( p less than 0.001 ) in the LTRA No group ( peak FEV1 improvements independent of concomitant LTRA use [ interaction p-value=0.6742 ] ).
Trough FEV1 ( difference from placebo ) was 90±46 mL ( p=0.052 ) in the LTRA Yes group and 93±25 mL ( p less 0.001 ) in the LTRA No group ( trough FEV1 improvements independent of concomitant LTRA use [ interaction p-value=0.5218 ] ).
In conclusion, once-daily Tiotropium Respimat added to ICS+LABA improves lung function in patients with severe symptomatic asthma, independent of initial LTRA use. ( Xagena )
Dahl R et al, AAAAI Meeting, 2014